Deciphering the Impact of Exposures From the Gut Microbiome-derived Molecular Complex in Human Health and Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 183
- 试验地点
- 4
- 主要终点
- Gut microbiota Characterization
研究概览
简要总结
The ExpoBiome project will analyze the impact of fasting on patients with Parkinsons's Disease (PD) or rheumatoid arthritis (RA) on a clinical level as well as the effect of fasting on their immune system and gut microbiota. ExpoBiome will combine metagenomics and other "omics" [meta-transcriptomics, meta-proteomics and (meta-)metabolomics], bioinformatic analyses and biostatistics under a systems biology framework to gain new mechanistic insights into microbiome-immune system interactions in the context of chronic diseases with inflammatory signatures.
Besides a one time crossectional study of healthy participants, patients with RA and PD a longitudinal fasting study with two arms (RA and PD) is planned.
详细描述
The human gut microbiome is a complex ecosystem, which contributes essential functions to human physiology. Changes to the microbiome are associated with several chronic diseases characterised by inflammation, including neurodegenerative and autoimmune diseases. Microbiome-derived effector molecules comprising nucleic acids, (poly)peptides and metabolites are present at high levels in the gut but have so far eluded systematic study. This gap in knowledge is limiting mechanistic understanding of the microbiome's functional impact on chronic diseases such as Parkinson's Disease (PD) and rheumatoid arthritis (RA). Here, for the first time a combination of advanced high-resolution methodologies will be integrated to comprehensively identify the constituents of this molecular complex and their impact on the human immune system. First, a quantitative, integrated multi-omic analysis on microbiome samples collected from healthy individuals and patients with newly diagnosed PD or RA will be performes.
Using contextualised prior knowledge (ExpoBiome Map) and machine learning methods, we will identify microbial molecules associated with condition-specific immunophenotypes. Second, the biomarker signature during a model clinical intervention (therapeutic fasting) will be validated and tracked to predict treatment outcomes. Third, microbes and molecules will be screened in personalised HuMiX gut-on-chip models to identify novel anti-inflammatory compounds. By providing mechanistic insights into the molecular basis of human-microbiome interactions, the project will generate essential new knowledge about causal relationships between the gut microbiome and the immune system in health and disease. By facilitating the elucidation of currently unknown microbiome-derived molecules, it will identify new genes, proteins,metabolites and host pathways for the development of future diagnostic and therapeutic applications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •One of the following diagnoses: rheumatoid arthritis (first diagnosis >6 weeks ago and <8 years), parkinson's disease OR healthy volunteer
- •Control ("healthy") individuals must be without any evidence of active, known or treated RA, without any evidence of active, known or treated central nervous system disease, and without a known family history of idiopathic PD
- •Arthritis in at least one joint
- •Control individuals should match the RA or PD individuals as closely as possible, especially their age, sex, and education
- •Present written declaration of consent
- •Consent to specimen collection and specimen use
- •Ability to understand the patient information and willingness to sign the consent form
排除标准
- •gout or proven bacterial arthritis
- •Psychiatric illness that limits understanding of the examination protocol (unable to consent)
- •BMI < 18.5
- •Pre-existing/current eating disorders (bulimia nervosa, anorexia nervosa) within the past 5 years.
- •Severe internal diseases (e.g. renal insufficiency with creatinine > 2mg/dl)
- •Participation in another study
- •Existing vegan diet or fasting within the past 6 months
- •Pregnancy or breastfeeding
- •Chronic inflammatory bowel disease
- •Use of antibiotics within the past 12 months
- •Presence of anemia
结局指标
主要结局
Gut microbiota Characterization
时间窗: Change over baseline to 12 months
Molecular typing of the gut microbiota using sequencing and high-throughput analysis from stool samples (metagenomics, metatranscriptomics, metaproteomics, metabolomics)
次要结局
- Insulin (mU/L)(Change over baseline to 12 months)
- TSH (mU/L)(Change over baseline to 12 months)
- Anti-cyclic citrullinated peptide (ACPA) (U/mL)(Change over baseline to 12 months)
- Fatty acid binding protein 2 (FABP2) (pg/mL)(Change over baseline to 12 months)
- Heart rate(Change over baseline to 12 months)
- Hannover Functional Ability Questionnaire (Funktionsfragebogen Hannover, FFbH-R)(Change over baseline to 12 months)
- Sociodemographic Measurements(Baseline)
- Alcalic Phosphatase in units per liter (U/L)(Change over baseline to 12 months)
- Abdominal circumference(Change over baseline to 12 months)
- MDS-UPDRS(Change over baseline to 12 months)
- Non Motor Symptoms Scale (NMSS)(Change over baseline to 12 months)
- Behavioral Factors(Change over baseline to 12 months)
- Creatinine in µmol per liter (µmol/L)(Change over baseline to 12 months)
- Resting blood pressure(Change over baseline to 12 months)
- Parkinson's Disease Questionnaire-39 (PDQ-39)(Change over baseline to 12 months)
- Hospital Anxiety and Depression Scale (HADS)(Change over baseline to 12 months)
- Dietary Behaviour(Change over baseline to 12 months)
- Bilirubine (total, direct, indirect in mg/dL)(Change over baseline to 12 months)
- Total protein in grams per liter (g/L)(Change over baseline to 12 months)
- Waist to Hip Ratio(Change over baseline to 12 months)
- Mood questionnaire (Profile of Mood States, POMS)(Change over baseline to 12 months)
- Behavioral Factors: smoking(Baseline)
- Expectation questions(Baseline)
- Estimated glomerular filtration rate (eGFR) in milliliter per minute (mL/min)(Change over baseline to 12 months)
- HbA1C (mmol/mol Hb, %)(Change over baseline to 12 months)
- High sensitive CrP (mg/L)(Change over baseline to 12 months)
- Fecal Calprotectin (µg/g)(Change over baseline to 12 months)
- Oral microbiota analysis in saliva(Change over baseline to 12 months)
- Body Mass Index (kg/m2)(Change over baseline to 12 months)
- Disease Activity Score 28 (DAS-28-CRP)(Change over baseline to 12 months)
- Health Assessement Questionnaire (HAQ)(Change over baseline to 12 months)
- Simplified Disease Activity Index Score (SDAI)(Change over baseline to 12 months)
- Parkinson's Disease Sleep Scale-2 (PDSS-2)(Change over baseline to 12 months)
- Non-motor symptoms questionnaire (NMSQ)(Change over baseline to 12 months)
- Stress questionnaire (Cohen Perceived Stress Scale, CPSS)(Change over baseline to 12 months)
- Quality of Life questionnaire (WHO-5)(Change over baseline to 12 months)
- Behavioral Factors: alcohol consumption(Change over baseline to 12 months)
- Hepatic transaminases (GPT, GOT) and Gamma glutamyl transpeptidase (y-GT)(Change over baseline to 12 months)
- Albumine in grams per liter (g/L)(Change over baseline to 12 months)
- Urea in milligrams per deciliter (mg/dL)(Change over baseline to 12 months)
- Rheumatoid factor (RF, IgM) (U/mL)(Baseline)
- Plasma Calprotectin (µg/g)(Change over baseline to 12 months)
- Urine metabolomics (10 ml midstream urine)(Change over baseline to 12 months)
- Differential blood count(Change over baseline to 12 months)
- Blood lipids and fasting glucose(Change over baseline to 12 months)
- IGF-1 (ng/mL)(Change over baseline to 12 months)
- Zonulin (ng/mL)(Change over baseline to 12 months)
- Phenotyping of immune cells(Change over baseline to 12 months)
研究者
Andreas Michalsen
Prof. Dr. med.
Charite University, Berlin, Germany